PMID- 17186341 OWN - NLM STAT- MEDLINE DCOM- 20071016 LR - 20181113 IS - 0941-1291 (Print) IS - 0941-1291 (Linking) VI - 37 IP - 1 DP - 2007 TI - Efficacy and limitations of natural killer cell depletion in cyclophosphamide-induced tolerance. PG - 24-9 AB - PURPOSE: We previously developed a cyclophosphamide (CP)-induced tolerance protocol, consisting of an intravenous injection of 1 x 10(8) donor spleen cells (SC) given on day 0 and an intraperitoneal injection of 200 mg/kg CP given on day 2. In the present study, we modified this protocol with natural killer cell (NK) depletion in recipient mice, and evaluated the efficacy of tolerance induction. METHODS: We used B10.D2 (H-2d; IE+) and B10 (H-2b; IE-) mice as both donors and recipients. The recipient mice were treated with donor SC, CP, and donor bone marrow cells (BMCs) with or without NK depletion. RESULTS: A higher level of mixed chimerism was achieved in the NK-depleted recipients. Survival of both the skin and heart donor grafts was significantly prolonged in the NK-depleted recipients. Donor reactive Vbeta11+ T cells were found at the same level as in untreated control mice. Pretreatment with recipient NK cell depletion was effective in inducing higher levels of donor mixed chimerism; however, permanent engraftment of donor bone marrow was not achieved. CONCLUSION: Survival of donor grafts was remarkably prolonged in the NK cell-depleted group, but transplantation tolerance could not be induced. Our results suggest that NK cell depletion in CP-induced tolerance conditioning has some effect on the induction of donor-specific tolerance. FAU - Shimizu, Ichiro AU - Shimizu I AD - Department of Cardiovascular Surgery, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan. FAU - Tomita, Yukihiro AU - Tomita Y FAU - Okano, Shinji AU - Okano S FAU - Iwai, Toshiro AU - Iwai T FAU - Kajiwara, Takashi AU - Kajiwara T FAU - Onzuka, Tatsushi AU - Onzuka T FAU - Tominaga, Ryuji AU - Tominaga R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070101 PL - Japan TA - Surg Today JT - Surgery today JID - 9204360 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, Surface) RN - 0 (Immunosuppressive Agents) RN - 0 (Lectins, C-Type) RN - 0 (NK Cell Lectin-Like Receptor Subfamily B) RN - 8N3DW7272P (Cyclophosphamide) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - Antigens, Surface/immunology MH - *Chimerism MH - Cyclophosphamide/*immunology MH - Heart Transplantation/immunology MH - Immune Tolerance/*immunology MH - Immunosuppressive Agents/*immunology MH - Killer Cells, Natural/*immunology MH - Lectins, C-Type/immunology MH - Mice MH - Mice, Inbred Strains MH - Models, Animal MH - NK Cell Lectin-Like Receptor Subfamily B MH - Skin Transplantation/immunology MH - Transplantation Immunology MH - Treatment Outcome EDAT- 2006/12/23 09:00 MHDA- 2007/10/17 09:00 CRDT- 2006/12/23 09:00 PHST- 2006/04/24 00:00 [received] PHST- 2006/06/04 00:00 [accepted] PHST- 2006/12/23 09:00 [pubmed] PHST- 2007/10/17 09:00 [medline] PHST- 2006/12/23 09:00 [entrez] AID - 10.1007/s00595-006-3329-z [doi] PST - ppublish SO - Surg Today. 2007;37(1):24-9. doi: 10.1007/s00595-006-3329-z. Epub 2007 Jan 1.